[Persistent and asymptomatic carriers of Australia antigen. A method for the evaluation of big series (author's transl)].
The existence of an increasing number of apparently healthy carriers of the HBsAg demands a specific assisting attitude which must be highly reliable without increasing health care expenses. With that purpose, 129 asymptomatic carriers without prior history of jaundice and/or alcohol abuse were studied. The following discriminant criteria were used: hepatomegaly, other physical evidence of liver disease, hypertransaminasemia, and sulfobromophthalein retention. The carrier was defined as healthy after two consecutive examinations disclosing no abnormalities at intervals of six months, which occurred in 108 patients (84 %). No patient underwent liver biopsy, but the examination was still normal after two years in all cases. The presence of one or more abnormal findings was an indication for liver biopsy in 21 patients (16 %), and the procedure was accepted by 11 (52 %). The efficiency of the selection method was evaluated according to the histologic findings. The most useful criteria were hypertransaminasemia and sulfobromophthalein retention, in this order.


Do in-vivo behaviors predict early response in family-based treatment for anorexia nervosa?
The aim of the study is to explore whether identified parental and patient behaviors observed in the first few sessions of family-based treatment (FBT) predict early response (weight gain of 1.8 kg by session four) to treatment. Therapy film recordings from 21 adolescent participants recruited into the FBT arm of a multi-site randomized clinical trial were coded for the presence of behaviors (length of observed behavior divided by length of session recording) in the first, second and fourth sessions. Behaviors that differed between early responders and non-early responders on univariate analysis were entered into discriminant class analyses. Participants with fewer negative verbal behaviors in the first session and were away from table during the meal session less had the greatest rates of early response. Parents who made fewer critical statements and who did not repeatedly present food during the meal session had children who had the greatest rates of early response. In-vivo behaviors in early sessions of FBT may predict early response to FBT. Adaptations to address participant resistance and to decrease the numbers of critical comments made by parents while encouraging their children to eat might improve early response to FBT.


Highly increased production of bone marrow-derived blood cells by administration of homologous interleukin-3 to rhesus monkeys.
Recombinant rhesus monkey interleukin-3 (IL-3) was administered to normal rhesus monkeys in graded doses ranging from 3 to 30 micrograms/kg/d subcutaneously for 30 consecutive days or given as a continuous intravenous infusion at a dose of 30 micrograms/kg/d for 16 days. After a lag phase of about 1 week, a highly increased, dose-dependent production of bone marrow-derived blood cells was observed, preceded by amplification of bone marrow hematopoietic progenitor cells. Simultaneously, peripheral blood progenitor cells rose. The increase included basophilic, eosinophilic and neutrophilic granulocytes, monocytes, and the erythrocyte and platelet lineages. Characteristically, a T-lymphocyte response was absent. It is concluded that IL-3 in vivo stimulates blood cell production from an immature, multipotent progenitor cell.


Relationships Between Anthropometry and Maximal Strength in Male Classic Powerlifters.
Several studies have determined the influence of physical characteristics on strength. The present quantified the relationships between anthropometry and maximal strength. Male classic powerlifters (n=59) were measured before a championship. Two-tailed Pearson correlation analysis was used. Powerlifters that presented higher relative maximal strength (RMS) in the squat and bench generally had higher body weight (BW), body mass index (BMI), torso circumference (C), waist C/height, torso C/height (r=0.26 to 0.49, p<0.05), and smaller lower leg length (L)/height and forearm L/torso C (r=-0.31 to -0.45, p<0.05) ratios. Powerlifters with a higher % of their deadlift on their total generally presented a smaller BW, BMI, body fat percentage (BF%), waist and torso C, trunk L, waist C/height, torso C/height, trunk L/height, waist C/hip C, thigh L/lower leg L, trunk L/thigh L ratios (r=-0.26 to -0.49, p<0.05) and higher lower leg L, lower leg L/height, reach/height, and forearm L/torso C ratios (r=0.32 to 0.51, p<0.05). Stepwise regressions revealed that a bigger torso positively predicted absolute maximal strength (AMS) in the squat (β=0.41, p=0.04), the bench (β=0.77, p<0.01), the deadlift (β=0.88, p<0.01) and the total (β=0.89, p<0.01), that a higher torso C/height ratio positively predicted RMS in the squat(β=0.48, p<0.01), the bench (β=-0.87, p<0.01) and the total (β=0.66, p<0.01), and that reach/height positively predicted RMS in the deadlift (β=0.37, p<0.01) and it's % on the total (β=0.31, p<0.01), but negatively predicted RMS in the bench (β=-0.25, p=0.02) and its % on the total (β=-0.24, p=0.04) As all of the stronger correlations came from AMS, powerlifters should focus on increasing AMS (weight lifted) instead of RMS (Wilks pts).


Three-dimensional graphene/Pt nanoparticle composites as freestanding anode for enhancing performance of microbial fuel cells.
Microbial fuel cells (MFCs) are able to directly convert about 50 to 90% of energy from oxidation of organic matters in waste to electricity and have great potential application in broad fields such as wastewater treatment. Unfortunately, the power density of the MFCs at present is significantly lower than the theoretical value because of technical limitations including low bacteria loading capacity and difficult electron transfer between the bacteria and the electrode. We reported a three-dimensional (3D) graphene aerogel (GA) decorated with platinum nanoparticles (Pt NPs) as an efficient freestanding anode for MFCs. The 3D GA/Pt-based anode has a continuous 3D macroporous structure that is favorable for microorganism immobilization and efficient electrolyte transport. Moreover, GA scaffold is homogenously decorated with Pt NPs to further enhance extracellular charge transfer between the bacteria and the anode. The MFCs constructed with 3D GA/Pt-based anode generate a remarkable maximum power density of 1460 mW/m(2), 5.3 times higher than that based on carbon cloth (273 mW/m(2)). It deserves to be stressed that 1460 mW/m(2) obtained from the GA/Pt anode shows the superior performance among all the reported MFCs inoculated with Shewanella oneidensis MR-1. Moreover, as a demonstration of the real application, the MFC equipped with the freestanding GA/Pt anode has been successfully applied in driving timer for the first time, which opens the avenue toward the real application of the MFCs.


Hypersensitive adverse drug reactions to glucosamine and chondroitin preparations in Australia between 2000 and 2011.
This study investigates spontaneous adverse drug reactions (ADRs) to glucosamine and chondroitin in the Australian population between 2000 and 2011, with a primary focus on hypersensitivity reactions. Case reports of ADR to glucosamine and chondroitin sent to the Therapeutic Goods Administration between 2000 and 2011 were obtained and analysed. The demographic information and severity of the ADR were recorded for individual ADR cases. These reactions were classified according to the Brown et al grading system for generalised hypersensitivity reactions. This included mild hypersensitivity reactions (generalised erythema, urticaria and angioedema) through to moderate hypersensitivity reactions (wheeze, nausea, vomiting, dizziness (presyncope), diaphoresis, chest or throat tightness and abdominal pain), and more severe reactions (hypotension, confusion and collapse). In this study of 366 ADRs to glucosamine and chondroitin preparations, 71.85% of cases (n=263) were found to have hypersensitivity reactions. Of these 263 cases, 92 cases were classified as mild (eg, pruritus, urticaria and lip oedema), 128 cases classified as moderate (such as dyspnoea, nausea and abdominal pain), and 43 cases classified as severe (including amnesia, gait disturbance, somnolence and hypotension). It is not clear whether the patients involved had a known shellfish allergy or underlying atopy. Results of this investigation support the need for clear labelling on glucosamine and chondroitin preparations to raise awareness of possible adverse events for those predisposed to allergy or atopy in response to shellfish.


Modifying soul food for the Dietary Approaches to Stop Hypertension diet (DASH) plan: implications for metabolic syndrome (DASH of Soul).
This article presents results of a community-based participatory study (DASH of Soul) designed to produce soul food that meets the nutrient criteria of the DASH diet plan. DASH of Soul was tested during a 10-month period with two sub-groups of low-income African American women: (1) a focus group cooking club recruited from among "early adopters" of a previous intervention; and (2) a broader peer group dinner club recruited through a health center serving the neighborhood of the focus group. Methods for the cooking club included 10 filmed cooking labs to: (a) modify traditional soul food (MSF) to reduce food energy, total fat, saturated fat, sugar, and sodium; (b) evaluate and improve upon sensory acceptability; (c) integrate acceptable MSF into the DASH diet plan (MS-DASH); (d) produce VHS- and DVD-formatted MS-DASH cooking shows. Methods for the dinner club included monthly participation in weekly promotional dinner meetings that featured the cooking show and a different DASH food group each month for 8 months. Based on computer software analysis, the nutrient composition of a sample MS-DASH menu developed by the cooking club was consistent with nutrient levels for the DASH diet plan. The authors concluded from the focus group interviews and intercept surveys that, with continued motivation, the potential is good for the study population to make MS-DASH a lifestyle choice, reducing their risks for diet-related diseases that cluster to comprise metabolic syndrome.


[The presynaptic action of muscle relaxants and cholinesterase inhibitors].
This is a review of literature dealing with the action of relaxants and cholinesterase inhibitors on the skeletal muscles. They act on the presynaptic motor nerve endings in the muscles and, depending on the experimental conditions, increase or inhibit the release of acetylcholine by the endings. According to the literature data, two types of acetylcholine receptors (AchR) exist on the endings of a motor nerve. The neuronal type of AchR is related to a negative feedback mechanism and their blockade increases the release of acetylcholine by the motor nerve ending. Blockade of the muscular-type AchR is related to a positive, feedback mechanism and inhibits the release of acetylcholine.


Coactivator recruitment: a new role for PAS domains in transcriptional regulation by the bHLH-PAS family.
Transcriptional regulation is dependent on layers of interactions between transcription factors and coactivators, controlling the specificity, temporal regulation, and extent to which transcriptional programs are executed. A key issue in the field of transcriptional regulation is to identify structural mechanisms by which transcription factors and coactivators build hierarchical protein assemblies. The basic helix-loop-helix Per-ARNT-Sim domain (bHLH-PAS) family of transcriptional regulators comprises both transcription factors and coactivators, which have different functions despite conserved domain architecture. Within this family, the tandem PAS domains typically mediate dimerization of the transcription factors, while C-terminal transactivation domains facilitate the dynamic interplay between transcription factors and coactivators. However, recent studies have shown that the modular PAS domains play an important role in regulating coactivator recruitment and oligomerization status. In this study, we provide a brief overview of the structural and functional studies that have identified a novel protein interaction interface on PAS domains utilized by both transcription factors and coactivators within the bHLH-PAS family.


Vasoplegia after heart transplantation: outcomes at 1 year.
Vasoplegia syndrome is a potentially life-threatening condition that can occur following cardiopulmonary bypass. Heart transplantation is a recognized risk factor for developing this vasodilatory state. The objective of this study was to determine the effects of vasoplegia syndrome on 1-year heart transplant outcomes. A retrospective review of orthotopic heart transplants at a single institution between November 2010 and December 2014 was performed. Of the 347 consecutive adult patients, 107 patients (30.8%) met criteria for vasoplegia syndrome. Preoperative factors and intraoperative variables were collected and compared between vasoplegia and non-vasoplegia cohorts. The incidence of postoperative complications, transplant rejection and patient survival within 1 year were evaluated. Demographics and preoperative medication profiles were similar in both groups, while mechanical circulatory support device use was associated with vasoplegia syndrome (30.8% vs 20.0%; P = 0.039). Perioperative characteristics such as longer cardiopulmonary bypass [165.0 (interquartile range [IQR] 74) min vs 140.0 (IQR 42.7) min; P < 0.001] and increased blood product usage (24.7 ± 17.2 units vs 17.7 ± 14.3 units; P < 0.001) were associated with vasoplegia. Non-vasoplegia patients were more likely to be extubated [42.9 (IQR 37.3) h vs 66.8 (IQR 50.2) h; P < 0.001] and discharged earlier [10.0 (IQR 6) days vs 14.0 (IQR 11.5) days; P < 0.001]. One-year patient survival (92.0% vs 88.6%; P = 0.338) and any-treated rejection rates (82.7% vs 84.3%; P = 0.569) were not significantly different between groups. Although vasoplegia syndrome was associated with an increase in perioperative morbidity, including greater mechanical ventilation time and hospital length of stay, no significant differences in survival or allograft rejection at 1 year was demonstrated.


Sites of [3H]taurine Uptake in the Rat Substantia Nigra in Relation to the Release of Taurine from the Striatonigral Pathway.
The autoradiographic localization of radiolabelled taurine taken up in the rat substantia nigra in vivo together with conditions of release of the [3H]taurine taken up into brain slices were studied to determine whether they are consistent with the hypothesis that taurine may act as a neurotransmitter in the striatonigral pathway. At the light microscopic level the main cellular elements that became radiolabelled following the injection of [3H]taurine into the substantia nigra could be identified as glial cells. Electron microscope autoradiography confirmed that a subpopulation of glial cells including astrocytes, pericytes, and oligodendrocytes were radiolabelled and that neuronal perikarya were not radiolabelled. In addition, axonal elements including both terminal and preterminal boutons were found to have silver grains overlying them and were thus considered to be radiolabelled. This was supported by a quantitative analysis of the distribution of the silver grains; whereas glial elements had a significantly higher number of grains associated with them than with any other structure, axonal elements had a significantly greater number of grains than dendritic structures. Release of the preloaded [3H]taurine from superfused slices of substantia nigra occurred in response to veratridine, was calcium-dependent and was sensitive to inhibition by high magnesium concentrations or tetrodotoxin. Following the destruction of neurons in the striatum by ibotenic acid injections, although the weight of the ipsilateral substantia nigra was reduced, the uptake of [3H]taurine was not altered. In contrast to this, the veratridine-stimulated release was markedly attenuated, implying that the destruction of striatal neurons causes the loss of sites in the substantia nigra from which exogenous taurine is released. These results add further support to previous suggestions that taurine might act as a neurotransmitter or neuromodulator in the striatonigral pathway.


A mutator phenotype in cancer.
We have proposed that an early step in tumor progression is the expression of a mutator phenotype resulting from mutations in genes that normally function in the maintenance of genetic stability. There is new and strong experimental evidence that supports the concept of a mutator phenotype in cancer. As technologies for chromosomal visualization and DNA advance, there are increasing data that human cancer cells contain large numbers of mutations. First, I will review the concept of a mutator phenotype. Second, I will present the recent evidence that individual cancer cells contain thousands of mutations. Third, I will explore potential target genes that are required for maintenance of genetic stability in normal cells and ask if they are mutated in cancer cells. Fourth, I will address the timing of a mutator phenotype; is it an early event during tumor progression? Do tumors already contain cells that harbor mutations rendering them resistant to most chemotherapeutic agents? Lastly, I will speculate on the theoretical and practical implication of a mutator phenotype in cancer and consider the possibility of cancer prevention by delay, i.e., a reduction in mutation rates early during carcinogenesis might slow the progression of tumors.


Psychometric properties of questionnaires on functional health status in oropharyngeal dysphagia: a systematic literature review.
Questionnaires on Functional Health Status (FHS) are part of the assessment of oropharyngeal dysphagia. To conduct a systematic review of the literature on the psychometric properties of English-language FHS questionnaires in adults with oropharyngeal dysphagia. A systematic search was performed using the electronic databases Pubmed and Embase. The psychometric properties of the questionnaires were determined based on the COSMIN taxonomy of measurement properties and definitions for health-related patient-reported outcomes and the COSMIN checklist using preset psychometric criteria. Three questionnaires were included: the Eating Assessment Tool (EAT-10), the Swallowing Outcome after Laryngectomy (SOAL), and the Self-report Symptom Inventory. The Sydney Swallow Questionnaire (SSQ) proved to be identical to the Modified Self-report Symptom Inventory. All FHS questionnaires obtained poor overall methodological quality scores for most measurement properties. The retrieved FHS questionnaires need psychometric reevaluation; if the overall methodological quality shows satisfactory improvement on most measurement properties, the use of the questionnaires in daily clinic and research can be justified. However, in case of insufficient validity and/or reliability scores, new FHS questionnaires need to be developed using and reporting on preestablished psychometric criteria as recommended in literature.


Effects of Prone Position and Positive End-Expiratory Pressure on Noninvasive Estimators of ICP: A Pilot Study.
Prone positioning and positive end-expiratory pressure can improve pulmonary gas exchange and respiratory mechanics. However, they may be associated with the development of intracranial hypertension. Intracranial pressure (ICP) can be noninvasively estimated from the sonographic measurement of the optic nerve sheath diameter (ONSD) and from the transcranial Doppler analysis of the pulsatility (ICPPI) and the diastolic component (ICPFVd) of the velocity waveform. The effect of the prone positioning and positive end-expiratory pressure on ONSD, ICPFVd, and ICPPI was assessed in a prospective study of 30 patients undergoing spine surgery. One-way repeated measures analysis of variance, fixed-effect multivariate regression models, and receiver operating characteristic analyses were used to analyze numerical data. The mean values of ONSD, ICPFVd, and ICPPI significantly increased after change from supine to prone position. Receiver operating characteristic analyses demonstrated that, among the noninvasive methods, the mean ONSD measure had the greatest area under the curve signifying it is the most effective in distinguishing a hypothetical change in ICP between supine and prone positioning (0.86±0.034 [0.79 to 0.92]). A cutoff of 0.43 cm was found to be a best separator of ONSD value between supine and prone with a specificity of 75.0 and a sensitivity of 86.7. Noninvasive ICP estimation may be useful in patients at risk of developing intracranial hypertension who require prone positioning.


[Clinical and epidemiological characteristics of hymenolepiasis in the Ivano-Frankovsk region].
Based on their retrospective epidemiological analysis and examination of 56 outpatient case histories, the authors have studied the clinical and epidemiological regularities of hymenolepiasis in the Ivano-Frankovsk region, which is characterized by: 1) its epidemic and familial pattern, mainly afflicting rural populations, young schoolchildren in particular; 2) high contagiousness and incidence of multiinvasions in the tense foci; 3) a number of the most typical syndromes identified in the clinical picture of helminthic infections, which may serve as criteria for selecting patients for laboratory studies.


Routine Cholesterol Tests and Subsequent Change in BMI Among Overweight and Obese Children.
In 2011, the National Heart, Lung and Blood Institute and American Academy of Pediatrics concluded that both familial and obesity-associated dyslipidemias increase cardiovascular risk and recommended universal cholesterol testing at ages 9 to 11. It remains unknown whether testing influences body mass index (BMI) trajectory, a key modifiable cardiovascular outcome. This quasi-experimental-matched cohort includes children aged 9 to 11 years completing well visits in a diverse primary care network from 2012 to 2014. Participants had baseline BMI ≥85th% and no prior cholesterol testing. Propensity score matching identified untested children similar to tested children on weight measures, practice site, sex, age, race, ethnicity, insurance, and well visit frequency. Change in BMI z-score was assessed over 18 months. Regression adjusted for residual confounding following matching. Data were analyzed in 2018. Matching improved balance between tested and untested children for all characteristics. The matched cohort of 1808 children was predominantly non-Latino black (48%) or non-Latino white (33%), and Medicaid insured (39%). Baseline BMI z-score was 1.88 for tested and 1.84 for untested children. Of tested children, 25% had cholesterol levels above the 2011 guideline's "acceptable" range. Two children received cholesterol lowering medications. Adjusted analysis found no difference in change in BMI z-score between tested and untested children (0.02, 95% confidence interval -0.01, 0.04). Individual risk assessment in the form of cholesterol testing is not associated with change in BMI trajectory among overweight and obese children. Though testing may identify familial hypercholesterolemia, results suggest testing does not change BMI trajectory, a key strategy to reduce cardiovascular risk.


Formation of electron strings in narrow band polar semiconductors
We show that linear electron strings may arise in polar semiconductors. A single string consists of M spinless fermions trapped by an extended polarization well of a cigar shape. Inside the string the particles are free although they interact with each other via Coulomb forces. The strings arise as a result of an electronic phase separation associated with an instability of small adiabatic polarons. We have found the length of the string which depends on dielectric constants of semiconductors. The appearance of these electron strings may have an impact on the effect of stripe formation observed in a variety of high- T(c) experiments.


Cytotoxicity of streptavidin-blocked biotinyl-ricin is retrieved by in vitro immunotargeting via biotinyl monoclonal antibody.
The streptavidin-biotin system has been used to immunotarget whole ricin to tumor cells in a system that overcomes ricin-nonspecific cytotoxicity. Biotin was linked to ricin via a disulfide-containing reagent, sulfosuccinimidyl-2-(biotinamido)ethyl-1,3'-dithiopropionate. The product, biotinyl-S,S-ricin (b-ricin), retained most of its in vitro cytotoxic activity against human epidermoid carcinoma (KB) cells. Complexing b-ricin to streptavidin resulted in greater than 99% loss of its cellular toxicity which is associated with loss of cell-binding activity. The streptavidin-b-ricin complex could, however, be targeted to KB cells via the biotinylated monoclonal antibody 108 which is specific to the epidermal growth factor receptor overexpressed on KB cells. The complex did not regain its activity if the specific antibody was not biotinylated or if the biotinylated antibody was of a different specificity. Streptavidin is thus used to block b-ricin, presumably due to a steric restraint of the streptavidin on the ricin B-chain, and to bridge it to biotinyl antibody recognizing the target cell. Avidin could not replace streptavidin in this system since a complex between b-ricin and avidin retained a major part (60%) of ricin cytotoxic activity. This is attributed to the nonspecific binding of avidin to cells in vitro, including the KB cells. It is suggested that b-ricin is blocked by both streptavidin and avidin, but once the complex gains access to the cell surface, its cytotoxic activity is specifically retrieved.


Staphylococcal enterotoxin C injection in combination with ascorbic acid promotes the differentiation of bone marrow-derived mesenchymal stem cells into osteoblasts in vitro.
Staphylococcal enterotoxin C injection is established as a clinical therapy for delayed healing or disunion of bone fractures. In the present study, the effects of staphylococcal enterotoxin C injection in combination with ascorbic acid (SEC-AA) on the differentiation of bone marrow-derived mesenchymal stem cells (MSCs) and their influences on the mineralization of osteoblasts were investigated. SEC-AA treatment induced increased levels of alkaline phosphatase activity in MSCs and increased numbers of alizarin red-stained calcified nodules, indicating enhanced differentiation of MSCs into osteoblasts. The findings demonstrated that SEC-AA promoted the differentiation of MSCs into osteoblasts and accelerated the cytopoiesis of osteoblasts. Our data provide a cytological model for bone fracture therapy aimed at shortening the time required for healing and improving the clinical outcome, and also provide a theoretical basis for inducible differentiation of MSCs, mineralization of osteoblasts and reconstruction of bone tissues.


Antiparallel Dynamic Covalent Chemistries.
The ability to design reaction networks with high, but addressable complexity is a necessary prerequisite to make advanced functional chemical systems. Dynamic combinatorial chemistry has proven to be a useful tool in achieving complexity, however with some limitations in controlling it. Herein we introduce the concept of antiparallel chemistries, in which the same functional group can be channeled into one of two reversible chemistries depending on a controllable parameter. Such systems allow both for achieving complexity, by combinatorial chemistry, and addressing it, by switching from one chemistry to another by controlling an external parameter. In our design the two antiparallel chemistries are thiol-disulfide exchange and thio-Michael addition, sharing the thiol as the common building block. By means of oxidation and reduction the system can be reversibly switched from predominantly thio-Michael chemistry to predominantly disulfide chemistry, as well as to any intermediate state. Both chemistries operate in water, at room temperature, and at mildly basic pH, which makes them a suitable platform for further development of systems chemistry.


Occurrence of phosphate acquisition genes in Prochlorococcus cells from different ocean regions.
The cyanobacterium Prochlorococcus is the numerically dominant phototroph in oligotrophic parts of the oceans. Recently, it was shown that the distribution of phosphate acquisition genes did not match the 16S rRNA phylogeny among isolates from this group but rather appeared related to phosphate availability where the strains had been isolated. To further understand adaptation to phosphate limitation in Prochlorococcus, the distribution of phosphate acquisition genes was investigated in different ocean regions and related to local ortho-phosphate concentration. In regions characterized by less than 0.1 microM phosphate, most Prochlorococcus cells contain genes involved in phosphate uptake, regulation and utilization of organic phosphates. In contrast, most of these genes are absent in regions with more than 0.1 microM phosphate with the exception of genes involved in transport of phosphate (phoE and pstABCS) and three genes of unknown function. This pattern of phosphate acquisition genes showed no significant correspondence to the distribution of rRNA phylotypes. In addition, it was demonstrated that several genes in a separate genomic island were commonly present in low-P sites while absent in high-P sites. Overall, this study further demonstrates a linkage between environmental conditions in the ocean and genome content of Prochlorococcus.


Serglycin proteoglycan is required for multiple myeloma cell adhesion, in vivo growth, and vascularization.
Recently, it was discovered that serglycin, a hematopoietic cell proteoglycan, is the major proteoglycan expressed and constitutively secreted by multiple myeloma (MM) cells. High levels of serglycin are present in the bone marrow aspirates of at least 30% of newly diagnosed MM patients. However, its contribution to the pathophysiology of MM is unknown. Here, we show that serglycin knockdown (by ∼85% compared with normal levels), using lentiviral shRNA, dramatically attenuated MM tumor growth in mice with severe combined immunodeficiency. Tumors formed from cells deficient in serglycin exhibited diminished levels of hepatocyte growth factor expression and impaired development of blood vessels, indicating that serglycin may affect tumor angiogenesis. Furthermore, knockdown of serglycin significantly decreased MM cell adhesion to bone marrow stromal cells and collagen I. Even though serglycin proteoglycan does not have a transmembrane domain, flow cytometry showed that serglycin is present on the MM cell surface, and attachment to the cell surface is, at least in part, dependent on its chondroitin sulfate side chains. Co-precipitation of serglycin from conditioned medium of MM cells using a CD44-Fc chimera suggests that CD44 is the cell surface-binding partner for serglycin, which therefore may serve as a major ligand for CD44 at various stages during myeloma progression. Finally, we demonstrate that serglycin mRNA expression in MM cells is up-regulated by activin, a predominant cytokine among those increased in MM patients with osteolytic lesions. These studies provide direct evidence for a critical role for serglycin in MM pathogenesis and show that targeting serglycin may provide a novel therapeutic approach for MM.


Rate of pull-out strength gain of dual-etched titanium implants: a comparative study in rabbits.
The purpose of this study was to investigate the rate of pull-out strength gain of an etched titanium implant surface. Rabbit tibiae were used to compare machined titanium and proprietary dual-etched titanium implants. Two custom cylindric implants (3 mm in diameter and 4 mm in length) were placed in each right anteromedial tibia in 31 rabbits. At weeks 1, 2, 3, 4, 5, and 8, the implants in 5 rabbits were subjected to failure shear loading in a pull-out test. For shear failure testing, each tibial segment was mounted in a precision alignment jig, and an Instron pull-out test was performed on each implant. Beginning at week 3, there was a statistically significant difference (P < .01) between the dual-etched and the machined implants. There was a significant increase in strength for dual-etched implants between week 5 and week 8, while the machined implants did not show an increase during this time interval. The etched implants maintained a significantly greater pull-out strength for the remainder of the study, with a 3.2-fold greater mean strength at 8 weeks, equivalent to 6 months in humans. At 3 weeks, the etched implant's strength exceeded the strength that the machined implant had achieved at 8 weeks. In short-term healing in the rabbit tibia, the dual-etched surface demonstrated a more rapid rate of pull-out strength gain than the machined surface and remained significantly stronger throughout the 8 weeks of the study.


The effects of digitoxin and its metabolites on the transmembrane potential and contractile characteristics of guinea-pig ventricle strips.
The effects of 10(-7) and 10(-6) M digitoxin, and some of its metabolites, digitoxigenin-bis-digitoxoside, digitoxigenin-mono-digitoxoside and digitoxigenin on the transmembrane potential and contractile characteristics of guinea-pig right ventricle strips were studied to define the role of the sugar side-chain in these cleavage products of digitoxin. Digitoxin and digitoxigenin produced their maximum inotropic responses, without induction of arrhythmias, at about 30 min. However, the bis and mono compounds produced arrhythmias within 12 min, so the inotropy recorded may not be the maximum response. Digitoxin with 3 sugar residues and the bis compound with 2 sugar residues produced a prolongation in the action potenital duration. In contrast, the mono compound with one sugar residue and the digitoxigenin with no sugar residue produced a shortening of the action potential duration. There may be a relationship between the number of sugar moieties and the action potential duration; digitoxin and its bis derivative increased the action potential duration and mono- and digitoxigenin decreased the action potential duration. There also appeared to be an unusual relationship between the number of sugar moieties and induction of arrhythmias; arrhythmogenicity occurred at the doses employed with only the bis- and mono-digitoxoside. Finally, there appeared to be no simple relationship between chemical structure and inotropic potency.


Studying personality and personality disorders among people in the Caribbean: advocating for an emic-etic approach.
This article discusses issues relevant to the examination of personality and personality disorder in contexts, such as the Caribbean, which are under-represented in this scholarship. The article argues that because normal personality is the standard against which definitions of non-normality (and at the extreme, disorder) are derived, a crucial first step in identifying personality disorder is clear and culturally relevant definitions of normal personality. Two key conceptual perspectives on personality development and manifestation are presented, followed by a brief exploration, using the etic traits approach, of the problematic nature of any one perspective on normal personality. The article argues for the need for combined emic-etic approaches to understanding normal and non-normal personality, particularly in under-represented contexts such as the Caribbean. It ends by offering concrete suggestions on developing, in the Caribbean, programmes of research committed to these tasks.


Influence of fermented faba bean flour on the nutritional, technological and sensory quality of fortified pasta.
Faba bean has gained increasing attention from the food industry and the consumers mainly due to the quality of its protein fraction. Fermentation has been recently recognized as the most efficient tool for improving its nutritional and organoleptic properties. In this study, faba bean flour fermented with Lactobacillus plantarum DPPMAB24W was used to fortify semolina pasta. Pasta samples including different percentages of fermented faba bean flour were produced at the pilot-plant level and characterized using an integrated approach for chemical, nutritional, technological, and sensory features. At a substitution level of 30%, pasta had a more homogeneous texture and lower cooking loss compared to 50% addition. The impact of faba bean flour addition on pasta technological functionality, particularly of the protein fraction, was also assessed by scanning electron microscopy and textural profile analysis. Compared to traditional (semolina) pasta and pasta containing unfermented faba bean flour, the nutritional profile (in vitro protein digestibility and nutritional indexes - chemical score (CS), sequence of limiting essential amino acids, Essential Amino Acid Index (EAAI), Biological Value (BV), Protein Efficiency Ratio (PER), and Nutritional Index (NI)) and the resistant starch content of pasta containing 30% fermented faba bean flour markedly improved, while the starch hydrolysis rate decreased, without negatively affecting technological and sensory features. The use of fermentation technology appears to be a promising tool to enhance the quality of pasta and to promote the use of faba bean flour.


Complex reaction networks in high temperature hydrocarbon chemistry.
Complex chemical reaction mechanisms of high temperature hydrocarbon decomposition are represented as networks and their underlying graph topologies are analyzed as a dynamic system. As model reactants, 1,3-butadiene, acetylene, benzene, ethane, ethylene, methane, methyl isobutyl ketone (MIBK) and toluene are chosen in view of their importance for the global environment, energy technologies as well as their quantum chemical properties. Accurate kinetic mechanisms are computationally simulated and converted to bipartite graphs for the incremental conversion steps of the main reactant. Topological analysis of the resulting temporal networks reveals novel features unknown to classical chemical kinetics theory. The time-dependent percolation behavior of the chemical reaction networks shows infinite order phase transition and a unique correlation between the percolation thresholds and electron distribution of the reactants. These observations are expected to yield important applications in the development of a new theoretical perspective to chemical reactions and technological processes e.g. inhibition of greenhouse gases, efficient utilization of fossil fuels, and large scale carbon nanomaterial production.


Development of appropriate fibrolytic enzyme combination for maize stover and its effect on rumen fermentation in sheep.
In vitro studies were undertaken to develop an appropriate fibrolytic enzymes cocktail comprising of cellulase, xylanase and β-D-glucanase for maize stover with an aim to increase its nutrient utilization in sheep. Cellulase and xylanase added individually to ground maize stover at an increasing dose rates (0, 100, 200, 400, 800, 1,600, 3,200, 6,400, 12,800, 25,600, 32,000, 38,400, and 44,800 IU/g DM), increased (p<0.01) the in vitro dry matter digestibility and in vitro sugar release. The doses selected for studying the combination effect of enzymes were 6,400 to 32,000 IU/g of cellulase and 12,800 to 44,800 IU/g of xylanase. At cellulase concentration of 6,400 IU/g, IVDMD % was higher (p<0.01) at higher xylanase doses (25,600 to 44,800 IU/g). While at cellulase doses (12,800 to 32,000 IU/g), IVDMD % was higher at lower xylanase doses (12,800 and 25,600 IU/g) compared to higher xylanase doses (32,000 to 44,800 IU/g). At cellulase concentration of the 6,400 to 32,000 IU/g, the amount of sugar released increased (p<0.01) with increasing levels of xylanase concentrations except for the concentration of 44,800 IU/g. No effect of β-D-glucanase (100 to 300 IU/g) was observed at lower cellulase-xylanase dose (cellulase-xylanase 12,800 to 12,800 IU/g). Based on the IVDMD, the enzyme combination cellulase-xylanase 12,800 to 12,800 IU/g was selected to study its effect on feed intake and rumen fermentation pattern, conducted on 12 rams (6 to 8 months; 20.34±2.369 kg body weight) fed 50% maize stover based TMR. The total volatile fatty acids (p<0.01) and ammonia-N concentration was higher in enzyme supplemented group, while no effect was observed on dry matter intake, ruminal pH and total nitrogen concentration.


Assessing the prosthetic needs of farmers and ranchers with amputations.
Farmers and ranchers experience disabling injuries each year of which amputations account for 11%. Anecdotal evidence suggests that current prostheses may not be meeting the needs of farmers and ranchers with amputations. To better understand those prosthetic needs, a descriptive qualitative study was used to gather data with an engineering perspective. Farmers with an upper- or lower-limb amputation were interviewed. Issues explored included current and past prostheses used, prosthetic failures, and ability to complete farm tasks using a prosthesis. Prosthetists providing services to this population were also interviewed to gain knowledge of specific devices and practises used in their geographic region. Interviews with 40 farmers and 26 prosthetists revealed several common themes related to prostheses including durability/utility, environment, adaptation, cost, and education. Farmers and ranchers with amputations often made modifications to their prostheses, farm equipment, and daily routines in order to return to their vocation. Farmers and ranchers with amputations have distinct prosthetic needs. Their return to farming can be facilitated by creating more durable, affordable, and adaptable prosthetic components. Our results can help guide design of more comprehensive surveys for further information gathering and new devices and establish best prosthetic practises for farmers and those in other physically demanding professions.


Validity and reliability of the Russian version of the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R).
The aim of this study is to elaborate a valid and reliable Russian version of the ALSFRS-R. Russian adaptation of the ALSFRS-R was applied twice in 50 ALS patients followed by the test-retest analysis with a 7-day interval between applications and internal consistency analysis. Test-retest analysis showed very strong correlation for all of the ALSFRS-R variables. The intra-class correlation coefficient was 0.83. The elaborated Russian version of the ALSFRS-R has shown to be comparable with the original English version of the scale.


Synergistic effects of germ cell expressed genes on male fertility in mice.
Over 200 genes have been shown to be associated with infertility in mouse models. However, knockout mice reveal unexpected functional redundancy of some germ cell expressed genes. Single null mutations in mouse genes encoding four male germ cell proteins, transition protein 2 (Tnp2), proacrosin (Acr), histone H1.1 (H1.1), histone H1t (H1t) and sperm mitochondria-associated cysteine-rich protein (Smcp) have been generated and analysed. Tnp2 is believed to participate in the removal of the nuclear histones and initial condensation of the spermatid nucleus. Proacrosin is an acrosomal protease synthesized as a proenzyme and activated into acrosin during the acrosome reaction. The linker histone subtype H1.1 belongs to the group of main-type histones and is synthesized in somatic tissues as well as in germ cells during the S-phase of the cell cycle. The histone gene Hist1h1t is expressed exclusively in spermatocytes and may have a function in establishing an open chromatin structure for the replacement of histones by transition proteins and protamines. Sperm mitochondria-associated cysteine-rich protein (Smcp) is a major structural element of the mitochondria in the midpiece of the sperm tail. Male mutant mice lacking any of these proteins show no apparent defects in spermatogenesis or fertility. To examine the synergistic effects of these proteins in spermatogenesis and during fertilization four lines of double knockout mice Hist1h1a/Mcsp, Hist1h1t/Mcsp, Tnp2/Mcsp and Acr/Mcsp were established. It was found that even when knockout mice are heterozygous for one allele (-/+) and homozygous for the other allele (-/-), mice were subfertile. Homozygous double knockout mice of all four lines are nearly infertile. However, in the four homozygous double knockout mouse lines, different characteristic abnormalities are prominently manifested: In Hist1h1a-/-/Mcsp-/- the migration of spermatozoa is disturbed in female genital tract, in Hist1h1t-/-/Mcsp-/- spermatozoa show morphological head abnormalities, in Tnp2-/-/Mcsp-/- the motility of sperm is affected, and in Acr-/-/Mcsp-/- the sperm-oocyte interaction is impaired. These findings indicate strongly that male germ cell expressed genes have synergistic effects on male fertility.


Subscales of alexithymia show unique pathways through reappraisal and suppression to anxiety, depression and stress.
The goal of this work was to explore associations of constituent factors of alexithymia on mental health and potential mediating effects of emotion regulation strategies, specifically suppression and reappraisal. Data were collected through the crowd-sourcing platform Amazon Mechanical Turk (MTURK). Three hundred seventy-seven individuals completed questionnaires related to distress (Depression Anxiety Stress Scales [DASS]), emotion regulation (Emotion Regulation Questionnaire [ERQ]) and Alexithymia (Bermond-Vorst Alexithymia Questionnaire [BVAQ]). Three mediation models were constructed for depression, anxiety and stress, with BVAQ subscales (verbalizing, identifying, emotionalizing, fantasizing, and analyzing) as predictors and ERQ subscales (suppression and reappraisal) as mediators. Results indicated 37.3 % variance in depression, 25.2 % variance in anxiety, and 35.3 % variance in stress was explained by each model. Direct associations revealed emotionalizing and fantasizing were negatively associated with depression, anxiety, and stress, while verbalizing was additionally associated with depression, identifying was additionally associated with anxiety, and all four BVAQ subscales were associated with stress. BVAQ subscales demonstrated negative associations with reappraisal and positive associations with suppression that mediated anxiety and depression. However, suppression did not mediate relationships between BVAQ subscales with stress. Findings support the importance of examining multiple factors of alexithymia and associations with emotion regulation strategies and distress.


On estimands arising from misspecified semiparametric rate-based analysis of recurrent episodic conditions.
Marginal rate-based analyses are widely used for the analysis of recurrent events in clinical trials. In many areas of application, the events are not instantaneous but rather signal the onset of a symptomatic episode representing a recurrent infection, respiratory exacerbation, or bout of acute depression. In rate-based analyses, it is unclear how to best handle the time during which individuals are experiencing symptoms and hence are not at risk. We derive the limiting value of the Nelson-Aalen estimator and estimators of the regression coefficients under a semiparametric rate-based model in terms of an underlying two-state process. We investigate the impact of the distribution of the episode durations, heterogeneity, and dependence on the asymptotic and finite sample properties of standard estimators. We also consider the impact of these features on power in trials designed to test intervention effects on rate functions. An application to a trial of individuals with herpes simplex virus is given for illustration.


The genome of Trypanosoma cruzi contains a constitutively expressed, tandemly arranged multicopy gene homologous to a major heat shock protein.
cDNA libraries have been constructed in the plasmid vector pUC18 with mRNA isolated from both epimastigotes and trypomastigotes of the Peru strain of Trypanosoma cruzi. Pools of randomly selected clones were analyzed by hybridization-selection-translation. Translation products were immunoprecipitated either with normal human sera or with sera from patients with Chagas' disease (chagasic sera), and the immunoprecipitates were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. With this approach, a cDNA clone (pEC5) was identified which encodes a portion of an 85,000-Mr polypeptide. A genomic clone was subsequently isolated (FG1) by using oligonucleotide probes derived from the DNA sequence of this cDNA clone. A portion of this clone was isolated and sequenced, and the coding region for the protein was identified. Computer analysis of the predicted protein sequence indicates that this protein is closely related to the 83,000-Mr heat shock protein (hsp83) of Drosophila melanogaster, the hsp90 of Saccharomyces cerevisiae, and the hsp90 of chicken. This gene is tandemly organized in the T. cruzi genome as a cluster of 6 to 10 copies.


Analysis of the distribution of epiphytic lichens on Cedrus libani in Elmali Research Forest (Antalya, Turkey).
In order to evaluate environmental factors limiting distribution of species, diversity of epiphytic lichens was studied in 34 sites along an altitudinal gradient from 1300 to 1900 m on north-facing and south-facing slopes of Elmali Cedar Research Forest (Antalya province, Turkey) regarding the dispersion of lichens in different tree-diameter classes (0-15 cm, 15-30 cm, 30-45 cm, 45-60 cm and >75 cm). The results showed that the relationship between diameter classes with the number of lichen species was R2=0.6022. The highest number of species was in the diameter class of 30-45 cm. There was a clear relationship between all parameters, diameter, altitude and aspect, with species richness. Changes in the community structure of the epiphytic lichen vegetation were detected along an altitudinal gradient revealing the highest species richness in the highest zone. The elevation affected both the number and the composition of the lichen communities and the relationship between the attitudinal zones with number of lichen species was designated as R2=0.6462. The number of species was higher in the north aspects than in the south aspects in all diameter classes. The species number depending on the altitude was also higher in the north-facing slopes than in the south-facing slopes.


Reversal of functional changes in the brain associated with obstructive sleep apnoea following 6 months of CPAP.
Obstructive sleep apnoea (OSA) is associated with an increase in the number of bursts of muscle sympathetic nerve activity (MSNA), leading to neurogenic hypertension. Continuous positive airway pressure (CPAP) is the most effective and widely used treatment for preventing collapse of the upper airway in OSA. In addition to improving sleep, CPAP decreases daytime MSNA towards control levels. It remains unknown how this restoration of MSNA occurs, in particular whether CPAP treatment results in a simple readjustment in activity of those brain regions responsible for the initial increase in MSNA or whether other brain regions are recruited to over-ride aberrant brain activity. By recording MSNA concurrently with functional Magnetic Resonance Imaging (fMRI), we aimed to assess brain activity associated with each individual subject's patterns of MSNA prior to and following 6 months of CPAP treatment. Spontaneous fluctuations in MSNA were recorded via tungsten microelectrodes inserted into the common peroneal nerve in 13 newly diagnosed patients with OSA before and after 6 months of treatment with CPAP and in 15 healthy control subjects while lying in a 3 T MRI scanner. Blood Oxygen Level Dependent (BOLD) contrast gradient echo, echo-planar images were continuously collected in a 4 s ON, 4 s OFF (200 volumes) sampling protocol. MSNA was significantly elevated in newly diagnosed OSA patients compared to control subjects (55 ± 4 vs 26 ± 2 bursts/min). Fluctuations in BOLD signal intensity in multiple regions covaried with the intensity of the concurrently recorded bursts of MSNA. There was a significant fall in MSNA after 6 months of CPAP (39 ± 2 bursts/min). The reduction in resting MSNA was coupled with significant falls in signal intensity in precuneus bilaterally, the left and right insula, right medial prefrontal cortex, right anterior cingulate cortex, right parahippocampus and the left and right retrosplenial cortices. These data support our contention that functional changes in these suprabulbar sites are, via projections to the brainstem, driving the augmented sympathetic outflow to the muscle vascular bed in untreated OSA.


Prognosis of spontaneous echocardiographic contrast in the thoracic aorta.
The aim of this study was to assess the predictive value of spontaneous echocardiographic contrast (SEC) detected in the thoracic aorta by transesophageal echocardiography (TEE) on intermediate-term cardiovascular morbidity and mortality. We studied 299 consecutive patients (aged 61 +/- 13 years) without aortic aneurysm or dissection, who underwent TEE in 1995 to 1996. Cardiovascular deaths and nonfatal events were recorded over a period of < or = 60 months. Left ventricular function was classified as preserved versus depressed according to ejection fraction values (>40% vs < or = 40%) on 2-dimensional echocardiography. SEC was identified in 35 patients (11.7%). During follow-up, 66 patients died (36 deaths were due to cardiovascular causes; 10 and 26 cardiovascular deaths occurred in patients with and without SEC, respectively [p <0.001]). Survival time was significantly reduced in patients with versus without SEC (28 +/- 18 vs 39 +/- 19 months, p = 0.0012). Multivariate analysis revealed that the presence of SEC doubled the odds for cardiovascular death and for the combined end point of cardiovascular death and events. There was a significant difference in survival distributions between patients with and without SEC between both genders (p <0.001). In patients with normal or mildly reduced left ventricular function, SEC was predictive of an adverse outcome, whereas this was not the case in patients with more severely depressed cardiac function. It is concluded that the presence of SEC in the thoracic aorta is associated with a high risk of cardiovascular events and/or death over intermediate-term follow-up.


Sensitivity of Transmission Raman Spectroscopy Signals to Temperature of Biological Tissues.
Optical properties of biological tissues can be influenced by their temperature, thus affecting light transport inside the sample. This could potentially be exploited to deliver more photons inside large biological samples, when compared with experiments at room temperature, overcoming some of difficulties due to highly scattering nature of the tissue. Here we report a change in light transmitted inside biological tissue with temperature elevation from 20 to 40 °C, indicating a considerable enhancement of photons collected by the detector in transmission geometry. The measurement of Raman signals in porcine tissue samples, as large as 40 mm in thickness, indicates a considerable increase in signal ranging from 1.3 to 2 fold, subject to biological variability. The enhancements observed are ascribed to phase transitions of lipids in biological samples. This indicates that: 1) experiments performed on tissue at room temperature can lead to an underestimation of signals that would be obtained at depth in the body in vivo and 2) that experiments at room temperature could be modified to increase detection limits by elevating the temperature of the material of interest.


[Scavenging effects of cyproheptadine on oxygen free radicals].
The scavenging effects of cyprohepdadine (Cyp), an antiserotonin-antihistaminic agent with significant calcium channel blocker activity, on oxygen free radicals were studied. Cyp was found to significantly scavenge the hydroxyl radical (.OH) produced by Fenton reaction (Fe(2+)+H2O2) (EC50 = 54 mumol/L) and inhibit the rate of .OH generation (IC50 = 22 mumol/L). The inhibitory effects of Cyp were significantly more potent than those of mannitol, a specific .OH scavenger, with EC50 of 22.7 mmol/L and 10.7 mmol/L respectively. Cyp was also shown to have certain scavenging effect on superoxide anion (O2-.) produced by peritoneal polymorphonuclear leukocytes (PMNs) in rats (IC50 = 179 mumol/L). These results suggest that the anti-myocardial injury activity of Cyp may be, at least partially, related to its scavenging effects on oxygen free radicals.


Oral immunization of a non-recombinant Lactococcus lactis surface displaying influenza hemagglutinin 1 (HA1) induces mucosal immunity in mice.
Mucosal immunization of influenza vaccine is potentially an effective approach for the prevention and control of influenza. The objective of the present study was to evaluate the ability of oral immunization with a non-recombinant Lactococcus lactis displaying HA1/L/AcmA recombinant protein, LL-HA1/L/AcmA, to induce mucosal immune responses and to accord protection against influenza virus infection in mice. The LL-HA1/L/AcmA was orally administered into mice and the immune response was evaluated. Mice immunized with LL-HA1/L/AcmA developed detectable specific sIgA in faecal extract, small intestine wash, BAL fluid and nasal fluid. The results obtained demonstrated that oral immunization of mice with LL-HA1/L/AcmA elicited mucosal immunity in both the gastrointestinal tract and the respiratory tract. The protective efficacy of LL-HA1/L/AcmA in immunized mice against a lethal dose challenge with influenza virus was also assessed. Upon challenge, the non-immunized group of mice showed high susceptibility to influenza virus infection. In contrast, 7/8 of mice orally immunized with LL-HA1/L/AcmA survived. In conclusion, oral administration of LL-HA1/L/AcmA in mice induced mucosal immunity and most importantly, provided protection against lethal influenza virus challenge. These results highlight the potential application of L. lactis as a platform for delivery of influenza virus vaccine.


Ascl3 knockout and cell ablation models reveal complexity of salivary gland maintenance and regeneration.
Expression of the transcription factor, Ascl3, marks a population of adult progenitor cells, which can give rise to both acinar and duct cell types in the murine salivary glands. Using a previously reported Ascl3(EGFP-Cre/+) knock-in strain, we demonstrate that Ascl3-expressing cells represent a molecularly distinct, and proliferating population of progenitor cells located in salivary gland ducts. To investigate both the role of the Ascl3 transcription factor, and the role of the cells in which it is expressed, we generated knockout and cell-specific ablation models. Ascl3 knockout mice develop smaller salivary glands than wild type littermates, but secrete saliva normally. They display a lower level of cell proliferation, consistent with their smaller size. In the absence of Ascl3, the cells maintain their progenitor function and continue to generate both acinar and duct cells. To directly test the role of the progenitor cells, themselves, in salivary gland development and regeneration, we used Cre-activated expression of diphtheria toxin (DTA) in the Ascl3-expressing (Ascl3+) cell population, resulting in specific cell ablation of Ascl3+ cells. In the absence of the Ascl3+ progenitor cells, the mice developed morphologically normal, albeit smaller, salivary glands able to secrete saliva. Furthermore, in a ductal ligation model of salivary gland injury, the glands of these mice were able to regenerate acinar cells. Our results indicate that Ascl3+ cells are active proliferating progenitors, but they are not the only precursors for salivary gland development or regeneration. We conclude that maintenance of tissue homeostasis in the salivary gland must involve more than one progenitor cell population.


Evaluation of the mouse mutant "wasted" as an animal model for ataxia telangiectasia. I. Age-dependent and tissue-specific effects.
The wasted mouse, an animal model proposed for the genetically transmitted human disease ataxia telangiectasia (AT), was examined for its biological, cytogenetic and biochemical properties. In affected homozygotes, a marked age-dependent decrease in the ratio of spleen and thymus to body weight, and a slight but significant decrease in the liver to body weight ratio were observed while no such change was found in the kidney. An age-dependent increase was observed in the frequency of both spontaneous and gamma-ray-induced chromosomal aberrations in bone marrow cells of wasted mice. In littermate control mice, neither of these alterations was observed in an age-dependent manner. The activity of a primer activating enzyme, which has been reported to be deficient in AT cells, also decreased with age in spleen cells, but not in liver cells of affected mice. However, alterations in apurinic DNA endonuclease activity were not detected in the developmental stages examined. These data indicate that this mouse mutant may serve as a useful animal model for studying the relationships between DNA repair and lymphoid tissue differentiation.


A review of the millipede genus Sinocallipus Zhang, 1993 (Diplopoda, Callipodida, Sinocallipodidae), with notes on gonopods monotony vs. peripheral diversity in millipedes.
The millipede genus Sinocallipus is reviewed, with four new cave-dwelling species, Sinocallipus catba, Sinocallipus deharvengi, Sinocallipus jaegeri and Sinocallipus steineri, being described from caves in Laos and Vietnam. With the new records the number of species in the genus reaches six and the genus range is extended to Central Vietnam and North and Central Laos. Both, Sinocallipus jaegeri from Khammouan Province in Laos and Sinocallipus simplipodicus Zhang, 1993 from Yunnan, China, show high level of reduction of eyes, which has not been recorded in other Callipodida. Peripheral characters such as the relative lengths of antennomeres, the number of ocelli, the number of pleurotergites or even the shape of paraprocts and the coloration seem to provide more information for the distinction of the species than do the relatively uniform gonopods. The differences in gonopods mainly concern the shape and length of cannula, the length and shape of coxal processes g and k, and the number of the acicular projections of the femoroid. An explanation is offered for the function of the trochanteral lobe of 9th leg-pair. It provides mechanical support for the cannula and seems to assist sperm charge and insemination during copulation. An identification key to the species in the genus is produced to accommodate the new species. The new species descriptions were automatically exported at the time of publication to a wiki (www.species-id.net) through a specially designed software tool, the Pensoft Wiki Convertor (PWC), implemented here for the first time together with a newly proposed citation mechanism for simultaneous journal/wiki publications.


Features and development trends of primary care research conducted by practice-based research networks from 1991 to 2023: a scoping review protocol.
Practice-based research networks (PBRNs) have been recognized as essential laboratories and mechanisms for developing primary care research. This scoping review aims to examine and map the features and development trends of productivity, research categories, and methods in original primary care research conducted by global PBRNs between 1991 and 2023. We have assembled an interdisciplinary team that will undertake this scoping review, following the framework developed by Arksey and O'Malley. Targeted literature includes original primary care research conducted by PBRNs, published from January 1, 1991, to December 31, 2023. An integrated search strategy will gather publications from 3 electronic databases (PubMed, Web of Science, and Embase), 16 major primary health care journals, and 364 relevant organizations. Two experienced researchers will independently screen the titles, keywords, and abstracts of all references and extract data regarding eight key elements. Disagreements between the reviewers will be resolved through group discussions, moderated by a third reviewer. Articles to be included will (1) be conducted in the primary care context, (2) be led by PBRNs, (3) provide a full report of original research, and (4) be published in a peer-reviewed journal between the aforementioned dates in any language. Exclusions encompass reviews, letters, commentaries, case reports, and conference papers. Final data will be displayed using tables and charts according to different conceptual categories. This scoping review is one of the initial attempts to delineate the development trends and features of primary care research conducted by PBRNs. This study will provide reference information for researchers in countries/regions that are building their research infrastructure and capacity in general practice, family medicine, and primary care. Registered in OSF on July 25, 2022 ( https://osf.io/zgv9c ).


microRNAs signatures as potential biomarkers of structural cardiotoxicity in human-induced pluripotent stem-cell derived cardiomyocytes.
Identification of early biomarkers of heart injury and drug-induced cardiotoxicity is important to eliminate harmful drug candidates early in preclinical development and to prevent severe drug effects. The main objective of this study was to investigate the expression of microRNAs (miRNAs) in human-induced pluripotent stem cell cardiomyocytes (hiPSC-CM) in response to a broad range of cardiotoxic drugs. Next generation sequencing was applied to hiPSC-CM treated for 72 h with 40 drugs falling into the categories of functional (i.e., ion channel blockers), structural (changes in cardiomyocytes structure), and general (causing both functional and structural) cardiotoxicants as well as non-cardiotoxic drugs. The largest changes in miRNAs expression were observed after treatments with structural or general cardiotoxicants. The number of deregulated miRNAs was the highest for idarubicin, mitoxantrone, and bortezomib treatments. RT-qPCR validation confirmed upregulation of several miRNAs across multiple treatments at therapeutically relevant concentrations: hsa-miR-187-3p, hsa-miR-146b-5p, hsa-miR-182-5p (anthracyclines); hsa-miR-365a-5p, hsa-miR-185-3p, hsa-miR-184, hsa-miR-182-5p (kinase inhibitors); hsa-miR-182-5p, hsa-miR-126-3p and hsa-miR-96-5p (common some anthracyclines, kinase inhibitors and bortezomib). Further investigations showed that an upregulation of hsa-miR-187-3p and hsa-miR-182-5p could serve as a potential biomarker of structural cardiotoxicity and/or an additional endpoint to characterize cardiac injury in vitro.


Contribution of functional voltage-gated Na+ channel expression to cell behaviors involved in the metastatic cascade in rat prostate cancer: I. Lateral motility.
Previous work suggested that functional voltage-gated Na(+) channels (VGSCs) are expressed specifically in strongly metastatic cells of rat and human prostate cancer (PCa), thereby raising the possibility that VGSC activity could be involved in cellular behavior(s) related to the metastatic cascade. In the present study, the possible role of VGSCs in the lateral motility of rat PCa cells was investigated in vitro by testing the effect of modulators that either block or enhance VGSC activity. Two rat PCa cell lines of markedly different metastatic ability were used in a comparative approach: the strongly metastatic MAT-LyLu and the weakly metastatic AT-2 cell line, only the former being known to express functional VGSCs. Using both electrophysiological recording and a motility assay, the effects of two VGSC blockers (tetrodotoxin and phenytoin) and four potential openers (veratridine, aconitine, ATX II, and brevetoxin) were monitored on (a) Na(+) channel activity and (b) cell motility over 48 h. Tetrodotoxin (at 1 microM) and phenytoin (at 50 microM) both decreased the motility index of the MAT-LyLu cell line by 47 and 11%, respectively. Veratridine (at 20 microM) and brevetoxin (at 10 nM) had no effect on the motility of either cell line, whilst aconitine (at 100 microM) and ATX II (at 25 pM) significantly increased the motility of the MAT-LyLu cell line by 15 and 9%, respectively. Importantly, at the concentrations used, none of these drugs had effects on the proliferation or viability of either cell line. The results, taken together, would suggest strongly that functional VGSC expression enhances cellular motility of PCa cells. The relevance of these findings to the metastatic process in PCa is discussed.


XY male pseudohermaphroditism in a captive Arabian oryx (Oryx leucoryx).
A 2-yr-old Arabian oryx (Oryx leucoryx) was presented for evaluation of abnormal genitalia and infantile behavior. The oryx had a penis and a scrotum, but testes were not palpable within the scrotum or inguinal canal. The total serum testosterone for the individual was lower than in age-matched males of the same species. Surgical exploration showed markedly hypoplastic intra-abdominal gonads, which demonstrated both testicular and uterine tissue on histologic examination. After karyotype analysis, the individual was classified as an XY male pseudohermaphrodite. This condition resembles two human intersex syndromes: embryonic testicular regression syndrome and partial gonadal dysgenesis syndrome, which occur in familial lines.


Temporal Dynamics of β-Amyloid Accumulation in Aging and Alzheimer Disease.
To understand the time course of β-amyloid (Aβ) deposition in the brain, which is crucial for planning therapeutic trials of Aβ-lowering therapies in Alzheimer disease (AD). Two samples of participants from the Alzheimer's Disease Neuroimaging Initiative were studied with [18F]Florbetapir (FBP) Aβ PET and followed for up to 9 years. Sample A included 475 cognitively normal (CN) older people and those with mild cognitive impairment (MCI) and AD and sample B included 220 CN Aβ- individuals. We examined the trajectory of FBP over time in sample A and the incidence rate of conversion from negative to positive Aβ PET scans in sample B. The relationship between time and brain Aβ was sigmoidal, taking 6.4 years to transition from amyloid negative to positive and another 13.9 years to the onset of MCI. Aβ deposition rates began to slow only 3.8 years after reaching the positivity threshold. The incidence rate for scan positivity was 38/1,000 person-years, and factors associated with conversion were age, baseline FBP, and being a female APOE ε4 carrier. Among CN Aβ- individuals, FBP slopes were associated with rates of memory decline and brain tau measured with [18F]Flortaucipir PET 5 years after baseline. Lowering brain Aβ must be accomplished early in the evolution of AD. Transitions of PET scans from Aβ- to Aβ+ should be predictable, and it is reasonable to expect that lowering rates of Aβ even in early stages could produce clinically significant benefits.


The effects of interventions preventing self-harm and suicide in children and adolescents: an overview of systematic reviews.
Background: Self-harm and suicide in children and adolescents are of serious consequence and increase during the adolescent years. Consequently, there is need for interventions that prevent such behaviour. The objective of this paper: to evaluate the effects of interventions preventing self-harm and suicide in children and adolescents in an overview of systematic reviews. Methods: We conducted a review of systematic reviews (OoO). We included reviews evaluating any preventive or therapeutic intervention. The quality of the included reviews was assessed independently, and data was extracted by two reviewers. We report the review findings descriptively. The certainty of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: Moderate certainty evidence suggests that school-based interventions prevent suicidal ideation and attempts short term, and possibly with long term effects on suicide attempts. The effects of community-based interventions following suicide clusters and local suicide plans are uncertain, as are the benefits and harms of screening young people for suicide risk. The effects of most interventions targeting children and adolescents with known self-harm are uncertain. However, low certainty evidence suggests that dialectical behavioural therapy and developmental group therapy are equally as effective on repetition of self-harm as enhanced treatment as usual. Conclusions: Research on several recommended practices, such as local suicide plans, prevention of suicide clusters and approaches to risk assessment, is lacking. When implemented, these interventions should be closely evaluated. There also is need for more research on treatment for repeated self-harm, including long term follow-up, and in general: possible harmful effects. Policy makers and health providers should consider evidence from population-based studies and adults in preventing self-harm and suicide in children and adolescents. Also, approaches showing promise in treatment of conditions associated with self-harm and/or suicidality, such as depression and psychosis, should be considered. PROSPERO registration: CRD42019117942 08/02/19.


The history and development of cardiac transplantation.
The history of heart surgery, spanning only 100 years to date, has seen some of the most daring and persistent men and women in all of medical history. Many aspects of heart surgery, including such innovations as the heart-lung machine, aortic aneurysm surgery, and the correction of congenital heart defects, have provided future surgeons with an important lesson: diligent research can solve complex problems. The history and development of cardiac transplantation is particularly full of challenges that have been overcome, with the research phase alone spanning more than 90 years. During that time, essential contributions came from all over the world, including the United States, Russia, England, and South Africa. As is typical of medical advancement, individual contributions did not stand alone but added to the experience of those who had come before. Even so, the work of a few particular groups deserves special recognition. Most notable is the Stanford team, led by Dr. Norman Shumway, who continued to transplant human hearts when other institutions had abandoned hopes for the operation. Largely because of the commitment of that team, cardiac transplantation has become a standard option in the treatment of end-stage heart disease. Currently, only the availability of donor hearts limits the number of cardiac transplantations performed worldwide.


[Prognostic factors of microalbuminuria in diabetes mellitus type 1].
The prophylaxis in diabetic nephropathy begin with the knowledge of factors that affect on the microalbuminuria. We designed a retrospective study with a follow-up of 8.4 +/- 2.9 years, in 75 patients with diabetes mellitus type 1: group A (n = 34) with microalbuminuria: group B (n = 41) without microalbuminuria. We tried to know the factors related to the on set of albuminuria. The mean Hb A1c was: Group A 8.7 +/- 1.5%; Group B 8.1 +/- 1% (p < 0.02). Patients that actually have microalbuminuria presented several years before a blood pressure (TA) greater than the group without microalbuminuria (Group A: TA systolic [TAS] 124.5 +/- 13 versus Group B 110.6 +/- 1 mmHg; p < 0.0001); (Group A: TA diastolic [TAD] 69.2 +/- 7 versus Group B 66.6 +/- 6 mm Hg; p < 0.0001). We confirm the influence of metabolic control on the microalbuminuria's beginning and the arterial blood pressure is greater in the group of patients with microalbuminuria actually.


The change from symmetry to asymmetry of a sodium transport system in red cell membranes.
A study has been made with human red cells of sodium movements that are sensitive to the drug furosemide. The aim was to see if furosemide-sensitive movements that are symmetrical (exchange) became asymmetrical (net transport) on replacement of chloride with nitrate as the major external anion. Cells were incubated for 4 h at 37 degrees C with 140 mM sodium, and chloride or nitrate as the principal anion. Under a variety of conditions (presence and absence of ouabain or furosemide, or both) the cell sodium concentration was always higher when chloride was replaced with nitrate. The cells became leakier to sodium. Tracer studies indicated that, in contrast to the results in chloride medium, the decrease in sodium influx was greater than the fall in efflux when furosemide was added to cells in nitrate medium. The results confirm that the sensitivity of sodium efflux to furosemide depended on chloride. However, influx showed a different sensitivity in that furosemide still inhibited in cells incubated in nitrate medium. The stimulation of sodium influx with nitrate medium was independent of external potassium (10-50 mM) and the furosemide-sensitive influx was also constant. It is concluded that symmetrical transmembrane sodium movements with cells in chloride medium became downhill asymmetrical in nitrate medium, giving a net gain of cell sodium that was insensitive to ouabain and sensitive to furosemide. The drug thus partly retarded the gain of cell sodium that otherwise occurred in the somewhat leaky cells.


[Raffinose metabolism in Gluconobacter oxydans].
Metabolism of raffinose has been examined in experiments with the growing culture and washed cells of Gluconobacter oxydans L-1. Degradtion of the trisaccharide was found to be catalyzed by levansucrase, levan being synthesized, and melibiose and small quantitites of fructose being liberated in the reaction. Melibiose is not hydrolyzed and is not used by the bacterium as a source of carbon, but is oxidized to melibionic acid. Fructose is assimilated by the bacterium in constructive metabolism, being oxidized to gluconic, 2-ketogluconic acids and 5-ketofructose.


Factors related to post-treatment chronic pain in breast cancer survivors: the interference of pain with life functions.
The frequency and the intensity of chronic pain, as well as the related factors, were assessed in a cohort of breast cancer patients. The life functions were also questioned in patients who have post-treatment chronic pain. The scope of this retrospective study was a cohort of surgically-treated breast cancer patients with unilateral early stage disease who were under regular follow-up. Patients were eligible if they completed their treatments at least 6 months before and were free of disease. Patients who had a previous history of chronic pain syndrome, chronic debilitating disease, psychiatric diagnosis, and other cancers were excluded. All data regarding their demographics and treatments were recorded. Chronic pain was defined as the pain at treatment-related regions for a duration of at least three months after completion of treatment. Turkish version of "Brief Pain Inventory (Short Form)" was given to the patients with chronic pain in order to assess their pain intensity and life functions. The factors related to chronic pain were compared between patients with and without chronic pain. Eighty-five eligible female patients were included in the study. Thirty-nine (46%) patients declared that they had chronic pain. The mean VAS scale score was 4.1 +/- 2.4 cm in these patients. The mean age of patients with chronic pain (54.3 +/- 12.6 years) was significantly less than that of the ones without pain (60.4 +/- 13.6 years; p = 0.035). Radiotherapy was found to be significantly related to chronic pain (p=0.049; OR: 2.60; 95% CI 1.07-6.30). The VAS scores were 1.5 +/- 2.7 cm, 1.9 +/- 3.2 cm, 1.3 +/- 2.7 cm, 0.9 +/- 2.5 cm for general activity, mood, relations with other people, and sleep, respectively. Although almost half of the early stage breast cancer patients experienced post-treatment chronic pain, they rated the intensity of their pain as mild to moderate. Younger age and receiving radiotherapy were found to be significant contributing factors. The interference of post-treatment chronic pain with life functions was small. Overall, mood was found to be the most affected life function among all.


Gas-liquid dispersion with dual Rushton turbine impellers.
Aerated and unaerated power consumption and flow patterns in a 0.56 m diameter agitated vessel containing water with dual Rushton turbines have been studied. Under unaerated conditions with a liquid height-to-diameter ratio of 2, an impeller spacing of 2 to 3 times the impeller is required for each to draw an amount of power equal to a single impeller. For aerated conditions, if a similar spacing is used, equations for the flooding-loading transition and for power consumption for a single Rushton impeller can be extended relatively easily to dual systems. All results for this spacing are explained by reference to bulk flow patterns and gassed-filled cavity structures and the proportion of sparged gas flowing through the upper impeller is also estimated. Such a spacing is generally recommended since it maximizes the power draw and hence the potential for oxygen mass transfer. Data are presented for other spacings but the results do not fit in easily with single agitator studies because strong impeller-impeller flow pattern interactions occur.


Dynamic optical coupled system employing even-numbered dammann gratings.
Dammann gratings are well known for their ability to generate arrays of uniform-intensity beams from an incoming monochromatic beam. We apply the even-numbered Dammann grating to achieve dynamic optical coupled technology. A 1 x N dynamic optical coupled system is developed by employing two complementary even-numbered Dammann gratings. With this system we can achieve a beam splitter and combiner as a switch between them according to the relative shift between the gratings. Also, this system is a preferable approach in integral packaging. More importantly, this device has the potential to be applied to the splitting of a large array, e.g., 8 x 16 array and 64 x 64 array, which is difficult to be realized with conventional splitting methods. We experimentally demonstrated a 1 x 8 coupler at the wavelength of 1550 nm. Furthermore we analyze the effects of the alignment errors between gratings and the wavelength-dependent error on efficiency and uniformity. The experimental results and the influence of alignment error and wavelength-dependent error are analyzed in detail.


Electro-optical fluorescence studies on the DNA binding of medically active drugs.
By measuring the transient changes in each of the polarized components of fluorescence during the application of a pulsed electric field to a solution of macromolecules, a method has been developed for evaluating the binding characteristics of fluorescent chemotherapeutic agents to DNA. It is shown that whereas quinacrine and berberine intercalate the DNA helix, hydroxystilbamidine does not. Furthermore, measurements on both the native and the diol-epoxide forms of benzo(a)pyrene show that the former is consistent with an intercalation type of binding, whilst the latter appears to be more inclined to the major DNA axis and may possibly be associated with the external helical grooves. The significance of these findings is discussed.


Transient Silencing of Antibiotic Resistance by Mutation Represents a Significant Potential Source of Unanticipated Therapeutic Failure.
Sporadic literature reports describe isolates of pathogenic bacteria that harbor an antibiotic resistance determinant but remain susceptible to the corresponding antibiotic as a consequence of a genetic defect. Such strains represent a source from which antibiotic resistance may reemerge to cause treatment failure in patients. Here, we report a systematic investigation into the prevalence and nature of this phenomenon, which we term silencing of antibiotic resistance by mutation (SARM). Instances of SARM were detected among 1,470 Staphylococcus aureus isolates through side-by-side comparison of antibiotic resistance genotype (as determined by whole-genome sequencing) versus phenotype (as assessed through susceptibility testing). Of the isolates analyzed, 152 (10.3%) harbored a silenced resistance gene, including 46 (3.1%) that exhibited SARM to currently deployed antistaphylococcal drugs. SARM resulted from diverse mutational events but most commonly through frameshift mutation of resistance determinants as a result of point deletion in poly(A) tracts. The majority (∼90%) of SARM strains reverted to antibiotic resistance at frequencies of ≥10-9; thus, while appearing antibiotic sensitive in the clinical microbiology laboratory, most S. aureus isolates exhibiting SARM will revert to antibiotic resistance at frequencies achievable in patients. In view of its prevalence in a major pathogen, SARM represents a significant potential threat to the therapeutic efficacy of antibiotics.IMPORTANCE Antibiotic resistance hinders the treatment of bacterial infection. To guide effective therapy, clinical microbiology laboratories routinely perform susceptibility testing to determine the antibiotic sensitivity of an infecting pathogen. This approach relies on the assumption that it can reliably distinguish bacteria capable of expressing antibiotic resistance in patients, an idea challenged by the present study. We report that the important human pathogen Staphylococcus aureus frequently carries antibiotic resistance genes that have become inactivated ("silenced") by mutation, leading strains to appear antibiotic sensitive. However, resistance can rapidly reemerge in most such cases, at frequencies readily achievable in infected patients. Silent antibiotic resistance is therefore prevalent, transient, and evades routine detection, rendering it a significant potential threat to antibacterial chemotherapy.


An improved one-tube RT-PCR protocol for analyzing single-cell gene expression in individual mammalian cells.
It is well known that gene expression is regulated at the level of individual cells, and more evidence is now emerging that heterogeneity of cell regulation is orders of magnitude greater than previously thought. In order to detect meaningful variations in transcription levels, it is necessary to measure gene expression at single cell levels rather than in bulk cells, where individual differences or heterogeneity could be lost. In this work, we report an improved reverse-transcriptase polymerase chain reaction (RT-PCR) protocol which allows the direct measurement of gene expression in one tube (5-25 microl of total PCR mixture) at the single mammalian cell level. The protocol employs a new cell lysis buffer, and involves no RNA isolation or nested PCR steps, significantly reducing the possibility of contamination and errors. We successfully applied this protocol in qRT-PCR and linear-after-the-exponential (LATE)-PCR to analyze selected genes of various expression levels from three cell lines. Although further characterization of RNA stability is important, the preliminary results showed that gene expression heterogeneity could be common among members of genetically identical cell populations. The protocol illustrated can be utilized for a wide array of applications without much modification, such as cancer cell analysis and preimplantation genetic diagnostics. In addition, the protocol is based on intercalator-based (SYBR Green PCR) chemistry, which is less expensive and suitable for high-throughput platforms.


Combined evaluation of multi-biomarkers and metal bioaccumulations in two different fish species (Sparus aurata and Chelon labrosus) from İzmir Bay, Türkiye (Aegean Sea): Spatial, temporal and tissue-specific approaches.
Biomarkers were investigated to assess the effects of metal accumulation in Sparus aurata and Chelon labrosus in the İzmir Bay. Fish were collected from the Inner and Outer Bays in November 2020 and May 2021. According to the metal and biomarker measurements found in the organs, it was observed that the levels were higher in the liver and gill tissues than in the muscle tissues. Significant differences between tissues were found for all metals and biomarkers. In addition, biochemical biomarkers were found to be significant predictors of metal bioaccumulation. Histological changes were observed in liver and gills in each species and location. Although the metal levels determined according to the health risk assessment were below the threshold limits, the As levels for the lifetime cancer risk were within the limits to be considered. In conclusion, this study will provide robust results for its related study area.


Low temperature increases capillary blood refill time following mechanical fingertip compression of healthy volunteers: prospective cohort study.
Capillary refill time has been accepted as a method to manually assess a patient's peripheral blood perfusion. Recently, temperature has been reported to affect capillary refill time and therefore temperature may interfere with accurate bedside peripheral blood perfusion evaluation. We applied a new method of analysis that uses standard hospital pulse oximetry equipment and measured blood refill time in order to test whether lowered fingertip temperature alters peripheral blood perfusion. Thirty adult healthy volunteers of differing races (skin colors) and age (young: 18-49 years and old: ≥ 50 years) groups were recruited. We created a high fidelity mechanical device to compress and release the fingertip and measure changes in blood volume using infrared light (940 nm). Capillary refill times were measured at the fingertip at three different temperature settings: ROOM TEMPERATURE, COLD by 15 °C cold water, and REWARM by 38 °C warm water. The COLD group has decreased fingertip temperature (23.6 ± 3.6 °C) and increased blood refill time (4.67 s [95% CI 3.57-5.76], p < 0.001). This was significantly longer than ROOM TEMPERATURE (1.96 [1.60-2.33]) and REWARM (1.96 [1.73-2.19]). Blood refill time in older subjects tended to be longer than in younger subjects (2.28 [1.61-2.94] vs. 1.65 [1.36-1.95], p = 0.077). There was a negative correlation (r = - 0.471, p = 0.009) between age and temperature. A generalized linear mixed-effects model revealed that lower temperature (OR 0.63 [95% CI 0.61-0.65], p < 0.001) rather than age (OR 1.00 [0.99-1.01], p = 0.395) was the independent factor most associated with increased blood refill time. Lowered fingertip temperatures significantly increase blood refill time which then returns to baseline when the fingertip is rewarmed. In our limited number of population, we did not find an association with age after the adjustment for the fingertip temperature.


Effects of a Short Video Physical Activity Program on Physical Fitness Among Physical Education Students.
The Brain Break (BB) short video program is designed to improve physical activity (PA), motor skills, and fitness in children. In this study, we examined the effects of an 8-week short video-based Brain Break (HOPSports Company) PA program within physical education (PE) lessons on fitness and fitness knowledge among students. We studied 62 fifth-grade students (experimental group = 28; control group = 34) in the Ankara, Turkey school district. The experimental group received PE lessons once per week for eight weeks with the BB PA program, with extra videos viewed at home three days per week, while the control group received routine PE lessons during this period. We collected student responses to the Fitness Knowledge Test for Children and the Fitnessgram Test Battery before and after the experimental BB program. Results revealed that the experimental group showed increased fitness and fitness knowledge compared to the control group, showing that the BB PA videos can increase fitness and fitness knowledge in students.


"Continuity of care" experiences in midwifery education: perspectives from diverse stakeholders.
At least 20 continuity-of-care experiences are compulsory for student midwives in Australia, but little is known about this learning component. This paper presents an analysis of continuity experiences in one Region, incorporating diverse stakeholder perspectives from student midwives, maternity managers and registered midwives, with the aim of better understanding and optimizing experiences. Qualitative methods were utilized, employing mainly focus groups. Participants included 15 student midwives from the Regional University, 14 midwives and six managers, employed at the Regional referral hospital. Four themes were identified in the data; "woman-centred care", "counting the cost", "mutual benefits" and "into the future". The significant benefits of student continuity-of-care experiences were outlined by all three participant groups. Continuity experiences for student midwives facilitated the development of a woman-centred focus in the provision of maternity care. While the experience was challenging for students it was beneficial not only to them, but to registered midwives, the maternity services, and ultimately childbearing women. In order to appropriately prepare midwives for existing and future maternity services, and to continue to meet women's needs in all service delivery models, we require midwives who are well grounded in a woman-centred care philosophy and have had exposure to various care models.


[The spectrum of extracellular proteins of staphylococci--the passport of a strain].
The possibility of detecting identical strains was analyzed by comparing extracellular protein spectra of Staphylococcus aureus strains from the collection of the L. A. Tarasevich Institute for Standardization and Control of Medical Preparations. Analysis of the findings confirms that S. aureus and other Staphylococci should be characterized by their protein spectra and this marker should be present in the certificate of the strain in collections. Protein spectrum determination is obligatory for production strains.


Extracellular osmiophilic oval bodies in the vagal and facial lobes of Carassius auratus (Teleostei-Cyprinidae).
During the study of ultrathins sections of the vagal lobes and the facial lobe of Carassius auratus (Teleostei Cyprinidae), by electron microscopy, extracellular oval or discoidal, very osmiophilic structures were found in the neuropil of the lobes. The structures measured approximately 73 nm long 58 nm wide, and 29 nm thick and were located within the extracellular spaces surrounding some glial and neural processes; they were closely apposed to the external membrane of these cells, sometimes forming a pavement like pattern. These structures, as far as we know, have not been previously described and their function is unknown.


Suicide gene therapy for hepatocellular carcinoma cells by survivin promoter-driven expression of the herpes simplex virus thymidine kinase gene.
The aim of this study was to investigate the selective killing effect of the herpes simplex virus-thymidine kinase/ganciclovir (TK/GCV) suicide gene system controlled by the survivin promoter on hepatocellular carcinoma (HCC) cells in vitro. Recombinant plasmid vectors driven by the survivin promoter were constructed. HepG2 HCC and LO2 normal human liver cells were transfected with the recombinant plasmids, green fluorescent protein (GFP)/pSURV, TK/pSURV and TAT-TK/pSURV. GFP expression was detected by fluoroscopy and flow cytometry (FCM). TK gene expression was detected using RT-PCR and western blot analysis. The selective killing effects after GCV application were evaluated by tetrazolium assay, FCM and western blot analysis. Statistical analysis was performed by ANOVA. After transfection with GFP/pSURV, TK/pSURV and TAT-TK/pSURV for 48 h, GFP expression was observed in the HepG2 cells, but not in the L02 cells and TK gene expression was evidently detected by RT-PCR and western blot analysis in the HepG2 cells. Three stably transfected cell lines (HepG2/pSURV, HepG2/TK/pSURV and HepG2/TAT-TK/pSURV) were successfully established. Compared with the HepG2/TK/pSURV group, a significant 'bystander effect' was observed in the HepG2/TAT-TK/pSURV group with the incorporation of unmodifed HepG2 cells at different ratios. Following transfection with TK/pSURV and TAT-TK/pSURV, the growth of HepG2 cells in the presence of GCV was markedly inhibited. This finding was further corroborated by FCM and immunoblot analysis revealed the repressed expression of proliferating cell nuclear antigen (PCNA). Our results showed that the plasmid vectors carrying the TK and TAT-TK fusion protein gene driven by the survivin promoter were successfully constructed and their specific expression in HepG2 cells provided the basis for the targeted gene therapy of HCC.


Closed claims review of anesthesia for procedures outside the operating room.
The demand for anesthesia services is increasing due to more complex procedures being performed outside the operating room. We reviewed the literature and closed malpractice claims in the American Society of Anesthesiologists' Closed Claims database to assess liability and injury associated with anesthesia for procedures outside the operating room (nonoperating-room anesthesia, n = 24) compared with intra-operative surgical anesthesia (operating room, n = 1927) claims. A higher proportion of patients in nonoperating-room anesthesia claims underwent monitored anesthesia care (58 vs. 6%, P < 0.001) and were at the extremes of age (50 vs. 19%, P = 0.003) than in operating room claims. Half of the nonoperating-room anesthesia claims occurred in the gastrointestinal suite. Inadequate oxygenation/ventilation was the most common specific damaging event in nonoperating-room anesthesia claims (33 vs. 2% in operating room claims, P < 0.001). The proportion of death was increased in nonoperating-room anesthesia claims (54 vs. 24%, P = 0.003). Nonoperating-room anesthesia claims were more often judged as having substandard care (P = 0.003) and being preventable by better monitoring (P = 0.007). Nonoperating-room anesthesia claims had a higher severity of injury and more substandard care than operating room claims. Inadequate oxygenation/ventilation was the most common mechanism of injury. Maintenance of minimum monitoring standards and airway management training is required for staff involved in patient sedation.